Extended interval (EI) dosing for immune checkpoint inhibitor (ICI) mono- or consolidation therapy initiated due to the COVID-19 pandemic led to a significant reduction in ICI-related site visits for ...patients with stage III and IV non–small cell lung cancer. Here we report the safety and efficacy compared to standard dose (SD) schedules.
In this retrospective analysis, patients who received ICI mono- or consolidation therapy, or adjuvant ICI therapy were assessed. Safety and efficacy of EI dosing with data of SD schedules were compared.
One hundred seventeen patients received EI dosing for ICI and 88 patients SD. Patient characteristics were comparable. We observed 237 adverse events in the EI dosing cohort versus 118 in the SD group (P= .02). Overall, there was no difference in the occurrence of grade ≥3 adverse events (EI dosing: 21/237 8.9%; SD group: 20/118 17.0%, P = .42), except for the pembrolizumab EI dosing cohort. Of all patients who received an EI dosing schedule, however, only 8 (6.8%) were reduced to SD because of toxicity. In 5 (4.3%) patients ICI was permanently stopped because of severe toxicity compared to 11 (12.5%) discontinuations in the SD group. Short-term treatment interruption occurred with similar frequencies in both groups. Progression-free survival and overall survival were comparable in patients receiving pembrolizumab and in those receiving adjuvant durvalumab. Progression-free survival and OS were better in the EI dosing cohort of nivolumab.
EI dosing for ICI did not lead to an increase of clinically relevant toxicities resulting in dose reduction and/or treatment discontinuation. Efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seems a safe and effective strategy.
Aim: Retrospective analysis of the safety and efficacy of extended interval dosing (EI) ICI compared to standard dose (SD) schedules. Results: 117 patients received EI dosing and 88 SD. In the EI dosing cohort was no increase in toxicity leading to dose reduction and/or discontinuation of treatment. Furthermore, efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seem a safe and effective strategy and should be continued also beyond the COVID-19 pandemic.
Aims.We present a comparison between independent computer codes, modeling the physics and chemistry of interstellar photon dominated regions (PDRs). Our goal was to understand the mutual differences ...in the PDR codes and their effects on the physical and chemical structure of the model clouds, and to converge the output of different codes to a common solution. Methods. A number of benchmark models have been created, covering low and high gas densities $n = 10^3,10^{5.5}$ cm-3 and far ultraviolet intensities χ = 10, 105 in units of the Draine field (FUV: 6 < $h\,\nu$ < 13.6 eV). The benchmark models were computed in two ways: one set assuming constant temperatures, thus testing the consistency of the chemical network and photo-processes, and a second set determining the temperature self consistently by solving the thermal balance, thus testing the modeling of the heating and cooling mechanisms accounting for the detailed energy balance throughout the clouds. Results.We investigated the impact of PDR geometry and agreed on the comparison of results from spherical and plane-parallel PDR models. We identified a number of key processes governing the chemical network which have been treated differently in the various codes such as the effect of PAHs on the electron density or the temperature dependence of the dissociation of CO by cosmic ray induced secondary photons, and defined a proper common treatment. We established a comprehensive set of reference models for ongoing and future PDR model bench-marking and were able to increase the agreement in model predictions for all benchmark models significantly. Nevertheless, the remaining spread in the computed observables such as the atomic fine-structure line intensities serves as a warning that there is still a considerable uncertainty when interpreting astronomical data with our models.
Aims.The physical conditions and chemical structure in the dark cloud of Barnard 5 and its surrounding atomic halo is studied. The impact of the halo on the line emission emerging from the molecular ...cloud is investigated.Methods.We present observations of the CI 3P$_1\rightarrow$ 3P0 transition of neutral carbon and the low-J transitions of 12CO and 13CO. The CO maps extend from the core ($A_{\rm v}\ga 7$) to the northern cloud edge and into the halo ($A_{\rm v}\la 1$). They are complemented by deeply integrated CI spectra made along a 1D cut of similar extent. Escape probability and photon-dominated region (PDR) models are employed to interpret the observations.Results.12CO and 13CO are detected in the cloud and the halo, while CI is detected only toward the molecular cloud. This occurs even though the neutral carbon column density is $\ga$5 times larger than the CO column density in the halo, but it can be understood in terms of excitation. The CI excitation is governed by collisions even at the low halo densities, while the CO excitation is dominated by the absorption of line photons emitted by the nearby molecular cloud. The upper limit on the neutral carbon column density in the halo is $6\times 10^{15}$ cm-2. The PDR studies show that even small column densities of H2 and CO, such as those in the B5 halo, can significantly change the CI and CO line emission (pre-shielding). Since this effect decreases the CI intensity and increases the CO intensity, the largest impact is noted for the CI/CO line ratios. For the B5 cloud, a PDR model with a molecular hydrogen column density of ~$6\times 10^{19}$ cm-2 in the halo matches the observed CI/CO line ratios best. Models with no pre-shielding, in contrast, suggest high gas densities that are in conflict with independently derived densities. The PDR models with a $\chi<1$ demonstrate that the CI/CO ratios cannot be attributed solely to a reduced FUV field.
Current knowledge of blunt cerebrovascular injuries (BCVIs) in craniomaxillofacial fracture (CMF) patients is limited. The purpose of this study was to determine the occurrence of BCVIs in patients ...with all types of CMF. This retrospective study included CMF patients in a level 1 trauma centre during a 3-year period. Patients who were not imaged with computed tomography angiography and patients with mechanisms other than blunt injury were excluded. The primary outcome variable was BCVI. A total of 753 patients were included in the analysis. A BCVI was detected in 4.4% of the patients screened. BCVIs occurred in 8.7% of cranial fracture patients, 7.1% of combined craniofacial fracture patients, and 3.1% of facial fracture patients. The risk of BCVI was significantly increased in patients with isolated cranial fractures (odds ratio (OR) 2.55, 95% confidence interval (CI) 1.18–5.50; P=0.017), those involved in motor vehicle accidents (OR 3.42, 95% CI 1.63–7.17; P=0.001), and those sustaining high-energy injuries (OR 3.17, 95% CI 1.57–6.40; P=0.001). BCVIs in CMF patients are relatively common in high-energy injuries. However, these injuries also occur in minor traumas. Imaging thresholds should be kept low in this patient population when BCVIs are suspected.
Aims.We use the Barnard 68 dark globule as a test case for a spherically symmetric PDR model exposed to low-UV radiation fields. With a roughly spherical morphology and an accurately determined ...density profile, Barnard 68 is ideal for this purpose. The processes governing the energy balance in the cloud surface are studied in detail. Methods. We compare the spherically symmetric PDR model by Störzer, Stutzki & Sternberg (1996) to observations of the three lowest rotational transitions of 12CO, 13CO J = 2 $\to$ 1, and J = 3 $\to$ 2, as well as the C i 3P1$\to$3P0 fine structure transition. We study the role of polycyclic aromatic hydrocarbons (PAHs) in the chemical network of the PDR model and consider the impact of depletion, as well as of a variation in the external FUV field. Results. We find it difficult to simultaneously model the observed 12CO and 13CO emission. The 12CO and C i emission can be explained by a PDR model with an external FUV field of 1-0.75 $\chi_0$, but this model fails to reproduce the observed 13CO by a factor of ~2. Adding PAHs to the chemical network increases the C i emission by 50% in our model but makes C ii very faint. The CO depletion only slightly reduces the 12CO and 13CO line intensity (by $\la$10% and $\la$20%, respectively). Predictions for the C i ${^2}$P3/2$\to$${^2}$P1/2, C i 3P2$\to$3P1, and 12CO J = 5 $\to$ 4 and 4 $\to$ 3 transitions are presented. This allows a test of our model with future observations (APEX, NANTEN2, HERSCHEL, SOFIA).
We present a numerical model for the simulation of water line emission in cometary coma. The model is based on a spherically symmetric density distribution with a constant expansion velocity (Haser ...model) and the Monte Carlo radiative transfer code published by Hogerheijde & van der Tak. It includes the seven lowest rotational levels of orthowater, which are the primarily populated levels in the rotationally cold gas of the coma. We discuss the main excitation mechanisms for ortho-water in the coma and study their relative contribution as a function of distance from the comet nucleus. The model is used to derive the water production rate from observations made with the Submillimeter Wave Astronomy Satellite toward comet C/1999 T1 (McNaught-Hartley). They differ from the water production rates derived with an independent model by less than 20% and thus agree within the larger uncertainty due to the limited signal-to-noise ratio of the observations. We give predictions for spectral line observations of H sub(2)O and H sub(2) super(18)O in comets with present and future airborne and space observatories, including ESA's Herschel Space Observatory and the Stratospheric Observatory for Infrared Astronomy (SOFIA). These models cover a range of water vapor production rates (10 super(27)-10 super(29) s super(-1)) and heliocentric distances (1-3 AU) and demonstrate that water line emission can be easily detected with Herschel.
We present a detailed study of the Δ-variance as a method to quantify molecular cloud structure. The Δ-variance was introduced by Stutzki et al. (1998) to analyze the drift behaviour of scalar ...functions and is used to characterize the spatial structure of observed molecular cloud images. For fractional Brownian motion structures ( fBm-fractals), characterized by a power law power spectrum and random phases, the Δ-variance allows to determine the power spectral index β. We present algorithms to determine the Δ-variance for discretely sampled maps and study the influence of white noise, beam smoothing and the finite spatial extent of the maps. We find that for images with $\beta> 3$, edge effects can bias the structure parameters when determined by means of a Fourier transform analysis. In contrast, the Δ-variance provides a reliable estimate for the spectral index β, if determined in the spatial domain. The effects of noise and beam smoothing are analytically represented in a leading order approximation. This allows to use the Δ-variance of observed maps even at scales where the influence of both effects becomes significant, allowing to derive the spectral index β over a wider range and thus more reliably than possible otherwise. The Δ-variance is applied to velocity integrated spectral line maps of several clouds observed in rotational transitions of 12CO and 13CO. We find that the spatial structure of the emission is well characterized by a power law power spectrum in all cases. For linear scales larger than ∼0.5 pc the spectral index is remarkably uniform for the different clouds and transitions observed ($2.5\le\beta\le2.8$). Significantly larger values ($\beta\ga3$) are found for observations made with higher linear resolution toward the molecular cloud MCLD 123.5+24.9 in the Polaris Flare, indicating a smoother spatial structure of the emission at small scales (<0.5 pc).
“Water and related chemistry in the Solar System” is a Herschel Space Observatory Guaranteed-Time Key Programme. This project, approved by the European Space Agency, aims at determining the ...distribution, the evolution and the origin of water in Mars, the outer planets, Titan, Enceladus and the comets. It addresses the broad topic of water and its isotopologues in planetary and cometary atmospheres. The nature of cometary activity and the thermodynamics of cometary comae will be investigated by studying water excitation in a sample of comets. The D/H ratio, the key parameter for constraining the origin and evolution of Solar System species, will be measured for the first time in a Jupiter-family comet. A comparison with existing and new measurements of D/H in Oort-cloud comets will constrain the composition of pre-solar cometary grains and possibly the dynamics of the protosolar nebula. New measurements of D/H in giant planets, similarly constraining the composition of proto-planetary ices, will be obtained. The D/H and other isotopic ratios, diagnostic of Mars’ atmosphere evolution, will be accurately measured in
H
2
O
and CO. The role of water vapor in Mars’ atmospheric chemistry will be studied by monitoring vertical profiles of
H
2
O
and HDO and by searching for several other species (and CO and
H
2
O
isotopes). A detailed study of the source of water in the upper atmosphere of the Giant Planets and Titan will be performed. By monitoring the water abundance, vertical profile, and input fluxes in the various objects, and when possible with the help of mapping observations, we will discriminate between the possible sources of water in the outer planets (interplanetary dust particles, cometary impacts, and local sources). In addition to these inter-connected objectives, serendipitous searches will enhance our knowledge of the composition of planetary and cometary atmospheres.